Rituximab therapy in adults with refractory symptomatic immune thrombocytopenia: Long-term follow-up of 15 cases [Refrakter semptomatik immün trombositopeni tanılı erişkinlerde rituksimab tedavisi: 15 olgunun uzun süreli izlemi]

PubMed ID: 27102929Objective: This paper prospectively evaluates the long-term follow-up [mean ± standard deviation (SD) duration: 89.7±19.4 months] data of 15 patients (13 females and 2 males) with refractory symptomatic immune thrombocytopenia (ITP) treated with rituximab. Materials and Methods: Rituximab was administered at 375 mg/m2 weekly for a total of 4 doses. Complete response (CR) was defined as a platelet count of ?100,000/mm3 and partial response (PR) as a platelet count of ?30,000/mm3 but less than 100,000/mm3. Early response (ER) and late response (LR) were defined as response within 42 days and after 42 days of initiation of rituximab therapy, respectively. Sustained response (SR) was defined as response lasting for at least 6 months. Results: Mean age (±SD) at the start of rituximab was 46.6±11.3 years. Mean platelet count (±SD) prior to rituximab treatment was 17,400±8878/mm3. The mean time (±SD) between rituximab therapy and response to rituximab in early responders and late responders was 1.8±1.3 weeks and 10±2.8 weeks, respectively. Mean durations (±SD) of ER and LR were 51±47.2 months and 6±4.2 months, respectively. Seven of the 15 patients (46.7%) showed an initial response to rituximab (5 ER and 2 LR). The rate of SR over 6 months was 26.7% (4/15). Among the responders to rituximab, 3 (3/7, 42.9%) maintained their response 1 year after rituximab treatment and 2 (2/7, 28.6%) had ongoing response 5 years after initiation of rituximab. Two of the 7 patients (28.6%) still maintained their response 98 months after initiation of rituximab. All 5 initial responders with subsequent relapse achieved response from subsequent treatment modalities (3 CR, 2 PR). Conclusion: Our data confirm, over a long period of observation, that rituximab is safe and effective in the management of patients with chronic refractory primary ITP. © 2017 by Turkish Society of Hematology

Effects of mutational combinations on philadelphia-negative myeloproliferative neoplasms

WOS: 000399199200015PubMed ID: 28360451Philadelphia-negative myeloproliferative neoplasms (MPNs) were first described 65 years ago. Yet, the molecular features of the disease have become of interest since 2005 following the identification of the JAK2V617F mutation.1 Between 90% and 98% of patients with polycythemia vera and about 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) harbor the JAK2V617F mutation.2 In recent years, additional genetic factors such as the mutations of IDH1/2, TET2, EZH2, ASXL1, and CALR have been identified in Ph-negative MPNs.3 However, the significance of mutational combinations on Ph-negative MPNs remains unknown

The clinical significance of IDH mutations in essential thrombocythemia and primary myelofibrosis

Background: Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). Methods: High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. Results: PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. Conclusions: We conclude that IDH mutations indicate a risk for leukemic transformation in PMF

The association of CMV infection with bacterial and fungal infections in hematopoietic stem cell transplant recipients: A retrospective single center study

This study aims to evaluate the probable association between CMV infection and bacterial or fungal infections in 91 consecutive adult patients who underwent autologous or allogeneic HSCT within a period of two years.Medical records of the patients were retrospectively reviewed. Blood cultures were evaluated by automated blood culture system. A quantitative real-time polymerase chain reaction was performed to detect CMV DNA.CMV infection and CMV disease were detected in 42 (46%) ADDIN EN.CITE <EndNote><Cite><Author>Ng</Author><Year>2005</Year><RecNum>191</RecNum><DisplayText>(Ng<style face="italic"> et al., </style>2005)</DisplayText><record><rec-number>191</rec-number><foreign-keys><key app="EN" db-id="a20etv5e6ade0berxf1vw5vp0apvfptetwwd" timestamp="1639991687">191</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ng, A. P.</author><author>Worth, L.</author><author>Chen, L.</author><author>Seymour, J. F.</author><author>Prince, H. M.</author><author>Slavin, M.</author><author>Thursky, K.</author></authors></contributors><titles><title>Cytomegalovirus DNAemia and disease: incidence, natural history and management in settings other than allogeneic stem cell transplantation</title><secondary-title>Haematologica</secondary-title></titles><periodical><full-title>Haematologica</full-title></periodical><pages>1672-1679</pages><volume>90</volume><number>12</number><dates><year>2005</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0390-6078</isbn><accession-num>WOS:000506833800012</accession-num><urls><related-urls><url><Go to ISI>://WOS:000506833800012</url></related-urls></urls></record></Cite></EndNote>(Ng et al., 2005) and six (6.6%) patients, respectively. Of the 158 microorganisms isolated, 115 (73%) were Gram-positive bacteria. Bacteremia and fungemia developed in 55 (60%) and eight (8%) patients, respectively. Concurrent CMV infection and bacteremia were detected in 17 (18.7%) patients and concurrent CMV infection and fungal infection were detected in five (5.5%) patients. Graft versus host disease (GVHD) developed in 15 (50%) allogeneic HSCT recipients and two (2.2%) autologous HSCT recipients. Twenty-one (23%) patients including 13 (43%) allogeneic and eight (13%) autologous HSCT recipients died.The most common infection is bacteremia, and it develops concurrently with CMV infection in approximately one-fifth of HSCT recipients. Gram-positive bacteria are more common in bacteremia. Further studies on the follow-up and treatment of infections after HSCT will improve survival rates post-HSCT

SECONDARY SOLID CANCER FREQUENCY AND RISK FACTORS IN PHILADELPHIA- NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Objective: Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) are characterized by clonal myeloproliferation and somatic mutations. Major complications of Ph-MPNs are thrombosis, bleeding, transformation to myelofibrosis and leukemia. One important concern in the course of Ph-MPNs is risk of development of secondary solid cancers (SSC). In a large cohort of Turkish Ph-MPN patients, we aimed to determine the types and frequencies of SSC, to identify risk factors for SSC including role of cytoreductive therapies and to study impact of SSC on survival in Ph-MPNs. Methodology: 1013 patients diagnosed with Ph-MPN from 1995 and 2022 under follow up at adult hematology sections of Istanbul Bakırköy Dr Sadi Konuk Hospital and Istanbul University Medical Faculty were included in this retrospective study. Results: Of the 1013 Ph- MPN patients enrolled in our study, 65, 46 and 37 patients were diagnosed with essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF), respectively. Patient clinical and laboratory characteristics are summarized in Table 1. Sixty-seven patients (6.6%) developed SSC, predominantly carcinoma (64.2%), non-melanoma skin cancer (23.9%), sarcoma (4.5%), and melanoma (3%). Median time to SSC diagnosis was 80.03 ± 60.5 months with no significant difference among Ph- MPN subtypes. Compared to patients with no diagnosis of SSC, patients with SSC were older at time of Ph- MPN diagnosis (63 vs. 54 years; p<0.001) and included a higher proportion of males (p=0.025). Ph- MPN patients with SSC and without SSC showed no significant difference for complete blood count parameters, spleen size, Ph-MPN diagnosis groups, driver mutation frequencies and follow-up time. Arterial thrombosis frequency was higher in patients with SSC (37.3% vs. 25.3%; p=0.030). SSC rates were 5.7% in patients not exposed to cytoreductive treatment and 5.3%, 4% and 2.1% with exposure to ruxolitinib, anagrelide, and interferon (IFN), respectively. A trend toward lower SSC rates was noted with IFN therapy (3% vs. 97%; p=0.066). SSC incidence was significantly higher in patients exposed to hydroxyurea (HU) as first-line monotherapy compared to other treatment groups (7.8% vs. 4.6%; p=0.046). Median OS in patients with SSC and patients with no diagnosis of SSC group were 273 months and 195 months, respectively. PV patients, who developed SSC, had significantly worse median OS compared to PV patients without SSC (Figure-1). Conclusion: The strengths of our study are that it enrolls a larger patient population, includes PV, ET and PMF subgroups, separately examines development of SSC after MPN, has a long follow-up period and has multicenter design. In MPN patients, malignancy screening gains more importance for those aged ≥65 and males. Our study evaluated with data from previous studies suggest that increased risk of developing SSC in MPN patients may be associated with cytoreductive therapy. Further studies with more pateints are needed to determine whether Ph- MPN patients are predisposed to development of SSC independent of cytoreductive therapy, to better assess risk of HU or RUX in promoting SSC development in MPNs, and to elucidate the potential protective effect of IFN

Hematopoietik kök hücre transplant alıcılarında CMV enfeksiyonu ile bakteriyel ve fungal enfeksiyonlar arasındaki ilişkinin değerlendirilmesi

Hematopoetik kök hücre transplantasyonu (HKHT), hematopoietik sistemin edinilmiş ve konjenital bozuklukları için yerleşik bir prosedür olup giderek artan bir şekilde kullanılmakta, ancak enfeksiyonlar morbidite ve mortaliteyi önemli ölçüde etkilemektedir. Bu çalışmada iki yıllık süreçte hastanemizde otolog (n=61) veya allogeneik (n=30) HKHT yapılan 91 olguda, önemli komplikasyonlar olan bakteriyemi ve CMV enfeksiyonu/hastalığı sıklığı, nakil sonrası seyir, diğer komplikasyonlar ve genel sağ kalım üzerine etkilerin araştırılması planlanmıştır. Bakteriyemi varlığını saptamak için ateşli hastalardan alınan kan kültürleri otomatik kan kültürü sisteminde incelenmiştir. CMV enfeksiyonu/hastalığı varlığını değerlendrmek için kullanılan CMV-DNA değerleri, kantitatif real-time PCR ile saptanmıştır. Nakilden sonraki ilk 100 gün boyunca haftada en az bir kez CMV-DNA takibi yapılmıştır. Klinik ve laboratuar verilerini içeren parametrelerin istatistiksel analiz ile değerlendirilmiştir.Hastalarda en sık rastlanan tanıların multiple myelom (% 54,9), akut myeloid lösemi (%13,2), non-Hodgkin lenfoma (%9,9) ve Hodgkin lenfoma (%5,5) olduğu belirlenmiştir. Allogeneik nakilli hastalarda vericilerin 18’i (%60) aile dışı, 12’si (%40) aile içi idi. Nakilde doku uyumu 22 hastada (%73,3) 10/10, yedi hastada (%23,3) 9/10 ve bir (%3,3) hastada 5/10 idi. Kemik iliği transplantasyonuna kadar geçen tanı zamanı otolog nakilli hastalarda 33 ± 44 ay (5-147) ve allogeneik nakilli hastalar için 37 ± 65 ay (3-326) olarak bulunmuştur. Kırk iki (% 46) hastada CMV enfeksiyonu, altı (% 6,6) hastada CMV hastalığı geliştiği saptanmıştır. HKHT yapılan hasta grubunda gelişen enfeksiyonlardan toplam 158 bakteriyel ve fungal patojen izole edilmiş, en sık izole edilen bakteri Gram pozitifler içinde metisiline dirençli koagülaz negatif stafilokoklar (MRKNS) (48, % 30), Gram negatifler içinde K. pneumoniae (16, % 10) olmuş ve bunu E. coli (8, % 5) takip etmiştir. Elli beş (%60) hastada bakteriyemi, sekiz (%8,8) hastada fungal enfeksiyon varlığı saptanmıştır. CMV enfeksiyonu, 17 (% 18,7) hastada bakteriyemiyle, beş hastada (% 5,5) fungal enfeksiyon ile eş zamanlı olarak ortaya çıkmıştır. Otolog nakilli ve allogeneik nakilli hasta grubunda bakteriyemi gelişme zamanı (otolog: 29 gün, allogeneik: 82 gün) anlamlı olarak farklı bulunmuştur (p=0,001). CMV-doku pozitifliği dört (% 4,4) hastada saptanmıştır. CMV enfeksiyonu sırasında kullanılan antiviral süresi, otolog (n=15, 22 gün) ve allogeneik nakilli (n=13, 40 gün) hastalar arasında anlamlı olarak farkı bulunmuştur (p=0,001). Allogeneik nakilli hastaların 15’inde (%50) ve otolog nakilli hastaların ikisinde (%2,2) GVHD geliştiği saptanmıştır. On üçü (%43) allogeneik, sekizi (%13) otolog olmak üzere 21 hasta (% 23) kaybedilmiştir. Ölümler % 8,8 oranında nüks ve %3,3 oranında sepsis nedeniyle gerçekleşmiştir. Sağ kalım analizlerinde CMV hastalığı olan gruptaki HKHT sonrası hastalık zamanı süresi (425 gün) ile CMV hastalığı olmayan gruptaki HKHT sonrası süre (586 gün) arasında anlamlı farklılık bulunmuştur (p=0,028). Allogeneik nakilli hastaların sağ kalım analizlerinde, CMV enfeksiyonu olan gruptaki HKHT sonrası hastalık zamanı süresi (511 gün) ile CMV enfeksiyonu olmayan gruptaki süre (286 gün) arasındaki fark istatistiksel olarak anlamlı olma eğilimindedir (p=0,063). HKHT sonrası enfeksiyöz komplikasyonlar, morbidite ve mortalitenin başlıca nedenleri olmaya devam etmektedir. HKHT yapılan hastalarda en sık gelişen enfeksiyon bakteriyemi olup hastaların yaklaşık beşte birinde CMV enfeksiyonu ile eş zamanlı gelişmiştir. Bakteriyemilerde Gram pozitif bakterilerin daha yaygın olduğu görülmekle beraber Gram negatif bakterilerde giderek artan çoğul direnç önem kazanmaktadır. HKHT hastalarında enfeksiyon hastalıklarını ve tedavisini irdeleyen daha fazla çalışmaya ihtiyaç vardır. Bu sayede HKHT hastalarında sağ kalım oranlarının iyileşmesi beklenmektedir

Hairy cell leukemia presenting with isolated skeletal involvement successfully treated by radiation therapy and cladribine: A case report and review of the literature.

İstanbul Bilim Üniversitesi, Tıp Fakültesi.We describe an unusual case of hairy cell leukemia (HCL) in a 55-year-old male presenting with isolated skeletal disease as the initial manifestation without abnormal peripheral blood counts, bone marrow involvement, or splenomegaly. To the best of our knowledge, there have been only two previous reports of a similar case. The patient presented with pain in the right femur. Anteroposterior radiographs of both femurs revealed mixed lytic-sclerotic lesions. PET scan showed multiple metastatic lesions on axial skeleton, pelvis, and both femurs. Histopathological examination of the bone biopsy revealed an infiltrate of HCL. Localized radiation therapy to both proximal femurs and subsequently 4 weeks later, a 7-day course of 0.1 mg/kg/day cladribine provided complete remission with relief of symptoms and resolution of bone lesions. We addressed the manifestations and management of HCL patients with skeletal involvement